Nanozymes in Upper Respiratory Tract Infections: Catalytic Mechanisms, Current Evidence, and Emerging Theranostic Strategies.

Abstract

Objective: This review evaluates nanozymes as catalytic biomaterials for upper respiratory tract infection (URTI)-related diagnosis, therapy, and prevention, with particular attention to differences in the maturity of evidence across these applications. The anatomically adjacent middle ear is also considered as a relevant model of biofilm-associated infection and barrier-limited local delivery. Methods: We reviewed studies involving respiratory pathogens, sinonasal disease, pharyngitis, intranasal vaccination, and otitis media. Evidence from other disease models was included only when it addressed a specific materials problem relevant to the upper airway, such as catalytic regulation, biofilm disruption, mucus transport, or local retention. Results: Diagnostic applications currently have the strongest evidence base, particularly for catalytic signal amplification in respiratory pathogen assays. In contrast, therapeutic evidence remains sparse and predominantly preclinical, with direct treatment studies in URTIs especially limited. Preventive applications are less extensively studied and are represented mainly by proof-of-concept intranasal influenza vaccination. Across these applications, performance depends on catalytic activity in protein- and mucus-rich media, biofilm penetration, control of pro-oxidant and antioxidant effects, and delivery to the intended anatomical site. Evidence from other anatomical sites provides useful design principles but should not be interpreted as evidence of efficacy in URTIs. Conclusion: Nanozymes should currently be regarded as engineerable catalytic biomaterials rather than clinically established anti-infective platforms for URTIs. Translation will require reproducible activity in airway-relevant environments, effective site-specific delivery, appropriate safety margins, and validation in disease-relevant models.